Burkholderia pseudomallei is a gram negative bacterium that is endemic to much of Southeast Asia and Northern Australia. It is an environmental saprophyte and is the cause of the human disease melioidosis; a severe pulmonary disease with high levels of mortality. In northeast Thailand melioidosis is responsible for at least 20% of all community acquired septicaemias and 40% of sepsis-related mortality. B. mallei is closely related to B. pseudomallei. It is the causative agent of glanders, a disease that usually affect horses and mules, although it can be highly virulent in humans. Both B. pseudomallei and B. mallei are considered potential bio-weapons and are classified as category B agents by the US Centers for Disease Control and Prevention.
B. pseudomallei infections can cause a myriad of symptoms and clinical manifestation of the disease may take decades following exposure. B. pseudomallei can invade both phagocytic and non phagocytic cell types employing a type III secretion system or a “molecular syringe” similar to that of Shigella flexneri. Once intercellular, B. pseudomallei is capable of cell to cell movement via actin based protrusions of the host cell. B. pseudomallei adheres to human epithelial cells lines but the mechanism for this adherence is unknown. Multiple type IV pilin genes have been identified in B pseudomallei, including a gene encoding the pilus structural protein, PilA. PilA appears to contribute to adherence of B. pseudomallei to culture respiratory cell lines and mutants of the gene BPSL0782 have some reduced virulence in BALB/C mice (Essex-Lopresti et al., 2005).
At present there is no effective vaccine that protects against infections by B. pseudomallei. A number of virulence factors have been identified in B. pseudomallei including a type III secretion system gene cluster, capsular polysaccharides, lipopolysaccharide (LPS), pili and flagella. Several of these have been used in subunit vaccines with very limited success. Attenuated mutants lacking various virulence factors have shown to be protective, although the use of a live attenuated mutant for human vaccination seems highly unlikely.
Preventing the colonization of host cells appears to be the most feasible approach to prevent infection, since once intercellular, B. pseudomallei is protected from many of the host immune mechanisms. A critical early stage in bacterial infections is the binding of the pathogenic organism via adhesins to the host receptor molecules. Exploiting bacterial adhesins would appear to be a possible strategy for protection from B. pseudomallei. 
Glycosaminoglycans form part of the extracellular matrix and are expressed on the surface of all eukaryotic cells. Microbial pathogens bind to proteoglycans, which consist of core proteins covalently linked to glycosaminoglycans or sulphated glycoconjugates. Glycosaminoglycans can be classified into different groups depending on the disaccharide repeat and the overall extent of sulphation: heparin, heparin sulphate, chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulphate, and keratan sulphate.
Bordetella as well as many other bacterial species utilize filamentous hemagglutinin (FHA) or similar proteins to adhere to sulphated glycoconjugates of respiratory mucus and the cell surfaces of epithelial cells. FHA is an extremely large protein, which is expressed as a 367 kDa precursor protein and processed both at the C and N terminal including cleavage of the C terminal third of the protein resulting in a 220 kDa mature protein. It has several binding domains including a RGD sequence involved in attachment to macrophages and a carbohydrate recognition domain. FHA has a specific glycosaminoglycan-binding or heparin-binding domain that has also been identified in the N-terminal region of the mature FHA. FHA is highly immunogenic and is both surface exposed and secreted. FHA along with inactivated pertussis toxin is a major component of the acellular pertussis vaccine, which is as effective as whole-cell DTP vaccines with fewer side effects.
In order to establish intercellular infections B. pseudomallei would require structures that adhere to eukaryotic cells. Identifying proteins that contain domains that have a glycosaminoglycan-binding domain or a heparin binding domain may allow for the identification of essential virulence factors. Generation of this protein or proteins in a recombinant system and using them as part of a subunit vaccine may provide protection from B pseudomallei. One such protein candidate is YP—111733, which has been cloned and expressed in a recombinant system. Using this purified protein with adjuvants has shown to be a very effective vaccine against lethal challenge by B. pseudomallei Ashdown.